ArticleGenes & development2008
Regulation of apoptosis by XIAP ubiquitin-ligase activity.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
103 citing papers in PubMed, 191 citations in OpenAlex.
- E3 ubiquitin ligase-mediated necroptosis: regulatory mechanisms and therapeutic implication in cancer.Molecular biology reports · 2026Review
- ARTS and small-molecule ARTS mimetics upregulate p53 levels by promoting the degradation of XIAP.Apoptosis : an international journal on programmed cell death · 2024Article
- USP36 inhibits apoptosis by deubiquitinating cIAP1 and survivin in colorectal cancer cells.The Journal of biological chemistry · 2024Article
- Sterigmatocystin induces autophagic and apoptotic cell death of liver cancer cells via downregulation of XIAP.Heliyon · 2024Article
- Murine Models of Familial Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- X-linked inhibitor of apoptosis protein represents a promising therapeutic target for relapsed/refractory ALL.EMBO molecular medicine · 2023Article
- Inhibition of Caspase 3 and Caspase 9 Mediated Apoptosis: A Multimodal Therapeutic Target in Traumatic Brain Injury.Current neuropharmacology · 2023Review
- The regulation of inhibitor of apoptosis proteins (IAPs) during the apoptosis ofFrontiers in physiology · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- XIAP as a multifaceted molecule in Cellular Signaling.Apoptosis : an international journal on programmed cell death · 2022Review
- The role of Ubiquitination in Apoptosis and Necroptosis.Cell death and differentiation · 2022Review
- Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?BBA advances · 2022Review
- Review
- The type III secretion system effector EspO of enterohaemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1.Cellular microbiology · 2021Article
- XIAP's Profile in Human Cancer.Biomolecules · 2020Review
- Regulation of Cell Death and Immunity by XIAP.Cold Spring Harbor perspectives in biology · 2020Review
- Cell death in animal development.Development (Cambridge, England) · 2020Review
- A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2.Cell death & disease · 2020Article
- Review
- Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Inhibitor of Apoptosis Proteins (IAPs) can bind to and inhibit caspases, the key executioners of apoptosis. Because IAPs are frequently overexpressed in human tumors, they have become major pharmacological targets for developing new cancer therapeutics. However, the precise physiological function of individual mammalian IAPs and their role as E3 ubiquitin-ligases in situ remain largely obscure. Here, we investigated the function of XIAP ubiquitin-ligase activity by inactivating the RING motif via gene targeting in the mouse. Removing the RING stabilized XIAP in apoptotic thymocytes, demonstrating that XIAP ubiquitin-ligase activity is a major determinant of XIAP protein stability. Surprisingly, the increased amounts of "XIAP-BIR-only" protein did not lead to attenuated but rather increased caspase activity and apoptosis. DeltaRING embryonic stem cells and fibroblasts had elevated caspase-3 enzyme activity, and XIAP DeltaRING embryonic fibroblasts were strongly sensitized to TNF-alpha-induced apoptosis. Similar results were obtained with XIAP deficient mice. Furthermore, deletion of the RING also improved the survival of mice in the Emu-Myc lymphoma model. This demonstrates a physiological requirement of XIAP ubiquitin-ligase activity for the inhibition of caspases and for tumor suppression in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.